The effects of alterations in alveolar PO2 and PCO2, edema, prostaglandins, sympathetic nerve stimulation, emboli and endotoxin were evaluated on the pulmonary vascular bed under conditions of controlled blood flow. Alveolar hypoxia and hypercapnia increased pulmonary vascular resistance in the intact lamb. The increase in vascular resistance was due to vasoconstriction in vessels upstream from small lobar veins, presumably the lobar arteries. The response to hypoxia and hypercapnia was not mediated by norepinephrine or histamine and did not involve systemic reflexes under the conditions of the present experiment. Pulmonary edema resulting from alloxan, saline infusion or venous obstruction did not increase pulmonary vascular resistance in the intact dog. Stimulation of the sympathetic nerves to the lung increased pulmonary vascular resistance by constricting lobar veins and vessels upstream in the precapillary bed. Studies with specific adrenergic blocking agents indicate that the response to nerve stimulation is due to activation of alpha receptors by norepinephrine released from nerve endings in the lobar vessels. Endotoxin and pulmonary emboli increase pulmonary vascular resistance in the intact dog. Studies in which the lung was perfused with dextran rather than blood indicate the factors in blood contribute to the pressor response to endotoxin and embolizaion. Prostaglandin F2 alpha increased pulmonary vascular resistance in the intact lamb, swine and dog; however, the site of vasoconstriction was found to be species-dependent. In contact, PGE1 dilated the pulmonary vascular bed in all 3 species.